This K02 application seeks continued support essential for my continued career development as a newly independent researcher of PET and SPECT neuroreceptor imaging in tobacco smokers. Through a K01 funded by NIAAA, I attained considerable expertise in the brain imaging of smokers with and without alcohol dependence. While conducting these studies, I realized the paucity of knowledge on the neuro-chemical consequences of tobacco smoking and decided to focus my future efforts predominantly in the field of tobacco smoking. I have demonstrated considerable research productivity as evidenced by my peer reviewed publications, my principal-investigatorship of a R01 (DA015577) and a primary project in the Yale Transdisciplinary Tobacco Use Research Center (TTURC). I have acquired significantly more administrative responsibilities in the past year, which will increase in 2006, thus, this K02 award is vital for providing 80% focused research time and for facilitating my maturation into a fully-independent investigator. Justification for the award is provided by a comprehensive 5-year Career Development Plan that fills important gaps and compliments my current expertise in SPECT/PET neuroreceptor imaging. Specifically, I will acquire specialized skills in: 1) image processing and analysis 2) mathematical modeling for neuroreceptor quantitation, 3) genetics, and 4) cognitive neuropsychology. Intensive training is provided by an integrated curriculum of intramural coursework, extramural didactics, individualized preceptorships, interactive symposia, and research-related organizational meetings. Two representative, funded research studies are included that address major hypotheses involving the role of the nicotinic acetylcholine receptor and the GABAA-benzodiazepine receptor in habitual tobacco smoking in humans. These investigations illustrate the impact this career award will have in furthering not only my scientific career, but also our fundamental understanding of the neurochemical mechanisms underlying habitual tobacco smoking. [unreadable] [unreadable] [unreadable]